Field of the invention
The present invention relates to a method for preparing a wound dressing material using a biopolymer and a wound dressing material using a biopolymer prepared thereby. The wound dressing material prepared according to the present invention can have excellent effects of inhibiting wound infections and preventing adhesions.
Related Art
A postoperative wound infection is one of the most common nosocomial infections, accounting for 38% of infections in all the infected patients. Based on the U.S. Center for Disease Control and Preservation (CDC) National Nosocomial Infection Surveillance (NNIS) system reports, surgical site infections (SSIs) are the third most common nosocomial infection, accounting for 14% to 16% of all nosocomial infections among hospitalized patients. Another report shows that about 27 million annual surgical procedures are performed and 675,000 SSIs occur in the US, and 30 million annual surgical procedures are performed and 900,000 SSIs occur in Europe. The SSIs act as a negative factor on the postoperative morbidity and recovery period, causing serious problems in patients, operators, and overall health care industries, resulting in an increased hospital length of stay and an increased medical insurance budget. Many countries have significantly reduced the SSI outbreak rate due to the development of surgical techniques and aseptic techniques over the years, but such progress has caused other problems, such as increasing resistant strains and increasing high-risk surgical patients. Especially, the risk of SSI was shown to increase in the surgery of patients with diabetes or obese, and the morbidity rate in this field is also a major concern for related workers. The World Health Organization expects that the number of diabetic patients to reach 300 million from 171 million in the year of 2010, and thus special attention is needed for SSI.
Among the endeavors to prevent SSI, in addition to strict aseptic environment and the application of surgery technique on the basis thereof, the use of antibiotics may be considered in view of the prevention. However, a direct intravascular administration of antibiotics for a long period of time may cause antibiotic resistance and the resultant toxicity risk, and thus a cautious approach is needed for the application of antibiotics. The appearance of products (Gentacoll® and Collatemp G®) for the local use, such as absorbable gentamicin-collagen implants (GCI), disclosed in U.S. Pat. No. 1,321,818 and US 2014/0038915 A1, may be helpful in solving such problems.
Rather than a direction injection, a local use of gentamicin may be performed at a significantly high concentration on the wound site, and on the contrary, gentamicin may be present at a relatively low concentration in the blood, and thus may reduce the risk of side effects or toxicity compared with the above-mentioned intravascular injection. In addition, these methods can anticipate an avoidance of the resistance problem caused by the administration of low concentrations of antibiotics for a long period of time, and an action of high-concentration gentamicin as a broad spectrum of antibiotic. Actually, it was verified that the gentamicin-resistant strains were killed with high-concentration local treatment, and it was reported that these products, which were used for the preventive or therapeutic purpose, reduced the risk of SSI in the surgical operations in several fields (cardiovascular and orthopedic surgery).
In addition, a postoperative adhesion refers to adhering of adjacent organs or tissues to each other, which need to be separated from each other, caused by fibrous tissues, which are excessively generated, and the blood, which flows out and coagulates, in the healing procedure of wounds, such as wounds from inflammations, wounds, friction, or surgery, and thus the postoperative adhesion may occur after all kinds of surgeries. Due to this, the organs or tissues around the operated site adhere to each other, causing serious clinical sequelae.
Generally, the incidence of postoperative organ adhesions is reportedly in a range of 55% to 93% (Ann. Royal Coll. Surg. Engl., 75, 147-153, 1993). A large percentage of abdominal surgeries result in adhesions. Although some of these adhesions may undergo spontaneous decomposition, but in most cases, the adhesion exists even after wound healing, causing a variety of sequelae. There are a variety of kinds of sequelae. The US statistical data show that postoperative adhesions entail, as main symptoms, 49% to 74% of enterocleisis, 15% to 20% of infertility, 20% to 50% of chronic pelvic pain, and about 19% of enterobrosia in a subsequent surgery (Eur. J. Surg., Suppl 577, 32-39, 1997).
The mechanism of intraperitoneal adhesion formation is specifically described in the paper published by Granger (Infert. Reprod. Med. Clin. North Am., 5:3, 391-404, 1994). According to Granger, adhesions are initiated by fibrin resulting from the clotting process of blood among exudates generated after surgeries. The inflammatory exudate is rich in fibrin which forms a clot of blood on wound surfaces. As fibrin is decomposed, mesothelium is regenerated, which normally results in wound healing. The decomposition of fibrin is dependent on the conversion of plasminogen into plasmin, which is a fibrinolytic enzyme, and this reaction is promoted by a tissue plasminogen activator (tPA) existing in the mesothelium and the underlying stroma. However, if the decomposition of fibrin does not occur, inflammatory cells and fibroblasts infiltrate into the fibrin matrix to result in organized adhesions. As described above, adhesions take place through a series of the fibrinogenesis mechanism and the fibrinolysis mechanism, and the relationship therebetween is not simple and is closely related to the healing process of wounds.
As one of various methods for preventing such adhesions, intensive research has been focused on an anti-adhesion agent that prevents the formation of adhesions between adjacent tissues, through the formation of a physical barrier during healing of wounds of tissues using a barrier, as similarly in the action of a surfactant. The anti-adhesion agents used for these barriers may be largely divided into two classes according to the morphology: one is a membrane type barrier including a film type, a non-woven type, and a sponge type, and the other is a solution type barrier including a gel type.
Examples of the membrane type anti-adhesion material include oxidized-regenerated cellulose, expanded polytetrafluoroethylene (hereinafter, referred to as “ePTFE”), films composed of modified hyaluronic acid, sodium carboxymethyl cellulose, and a chemical cross-linking agent, and the like. Examples of the solution type anti-adhesion material include a lactated Ringer's solution, a dextran-70 solution, a heparin solution, a sodium carboxymethyl cellulose solution, a hyaluronic acid solution, a chondroitin sulfate solution, a polyethylene glycol solution, a poloxamer solution, and the like. Among these solution type anti-adhesion materials, the lactated Ringer's solution, dextran-70 solution, heparin solution, and the like, have a main mechanism in which, during healing of the peritoneum, the fibrin-covered surfaces are floated each other. Although the materials are preparations which have been used to inhibit adhesions by separating tissues from each other, satisfactory anti-adhesion effects are not obtained due to their rapid absorption into the peritoneum (Am. Surg., 63, 775-777, 1983). Since polyethylene glycol and the like are not decomposed in vivo, only a low-molecular weight material, which can be discharged through a metabolic pathway at the time of absorption, may be used. However, the use of such a low-molecular weight material results in excessively rapid absorption, so that it cannot serve as an effective barrier to prevent adhesions for an extended period of time.
Meanwhile, hyaluronic acid disclosed in U.S. Pat. No. 4,141,973 is a linear macromolecular polysaccharide composed of alternately bonded β-D-N-acetylglucosamine and β-D-glucuronic acid, and is known to exhibit excellent biocompatibility even when it is transplanted or infused in vivo. However, also due to in vivo decomposition and absorption within a relatively short period of time, there is a limitation in terms of performance as an anti-adhesion agent. As an attempt to improve such disadvantages, U.S. Pat. No. 6,387,413 B1 discloses a hyaluronic acid gel composition prepared by adding a polymer compound, such as carboxymethyl cellulose, for the purpose of supplementing physical properties of hyaluronic acid gel per se. Although the materials that have developed until now show potentialities for the prevention of adhesions, since the chemical cross-linking method is mainly employed, there are problems associated with inconveniences of removing cross-linking agents or additives, complicated processes, and toxicity and safety.
Meanwhile, collagen is one of the most abundant proteins on the earth, and can be extracted from almost all biological organisms. The collagen mainly used in the tissue engineering is extracted from the bovine skin or muscle or porcine skin. However, collagen itself is a protein involved in the immune response, and the collagen, of which the immune response is minimized through the removal of telopeptide, also has a helical structure, but the amino acid sequence or the like on the collagen surface is reported to cause an immune response, and moreover, the scientific base that bovine-derived collagen has complete safety against bovine spongiform encephalopathy (BSE) factor is not sufficient.